Mast Cell Activation Syndrome (Part 1)

Today’s topic is about a condition called, Mast Cell Activation Syndrome (MCAS). I will start with some basic science information followed by a Q & A section later in this post with Matthew Hamilton, MD, a gastroenterologist from the Brigham and Women’s Hospital (BWH) in Boston, Massachusetts. Dr. Hamilton specializes in the diagnosis and treatment of mast cell disorders involving the gastrointestinal tract and is an integral part of the Mastocytosis Center at BWH. (Incidentally, I did my dietetic internship and spent the first 7 years of my career in the field of nutrition at BWH in Boston). 🙂

Because of the complexity of Mast Cell Activation Syndrome (MCAS), I will discuss this topic in a 3-part series. The first part of this series, I will briefly introduce the topic of mast cell disorders with a focus on MCAS. There is a broad spectrum of mast cell activation disorders from the rare disorder of systemic mastocytosis and monoclonal mast cell activation syndrome (MMAS) to a spectrum of mast cell disorders including MCAS. Mastocytosis is defined by an abnormal amount of mast cells that accumulate in many tissues in the body including bone marrow and the skin. Mast cell activation syndrome typically presents in individuals with a normal amount of mast cells.

There are some red flags that occur in patients that visit my digestive health nutrition practice that prompt me to have them follow up with their PCP or GI doctor to discuss the possibility of a mast cell disorder. In my experience, patients present with several of the below symptoms along with their GI complaints:

A noted uptick in the above symptoms may occur with stress– (stress releases corticotropin releasing factor which in turns can activate mast cells).

Let’s start with the basics:

What are mast cells? Mast cells are immune cells that function as “guards” for our innate and adaptive immune system. They respond to triggers of external or internal stress or danger. Mast cells reside anywhere the body interfaces with the environment such as in the skin, GI tract, urinary tract, lungs etc. Using the most simplistic illustration imagine that mast cells are like tiny water balloons that are filled with inflammatory chemicals that release into the body when the mast cells are activated.

In the medical literature, you will read about mast cell degranulation–which, in essence, is when the mast cells are ‘activated’ and release numerous bioactive substances (histamine, enzymes, heparin) pre-formed in granules and other compounds (cytokines, chemokines, nitric oxide, prostaglandins and more). These chemical substances can be vasoactive (may increase or decrease diameter of blood vessels leading to an increase or decrease in blood pressure and heart rate) and include proinflammatory mediators.

What activates mast cells? Allergens, bacteria, drugs, fungus, toxins, viruses and stress can lead to mast cell activation. There are a number of drugs that can trigger mast cells such as vancomycin, morphine, NSAIDs (such as Advil, ibuprofen), and muscle relaxants. Bear in mind, ‘normal’ levels of mast cell activation is common and necessary. The problem lies when mast cell activation is disordered. This can occur when there are too many mast cells or mast cells activate more readily than the necessary.

What are the symptoms one might experience with mast cell activation?

Mast cell activation can be localized or occur in multiple places in the body (systemic). Localized mast cell activation may appear as uticaria (hives) or wheezing. A more broad range of mast cell activation can impact multiple organs and include GI distress (nausea, vomiting, diarrhea, GERD) as well as uticaria or angioedema (swelling) and/or wheezing.

What makes mast cell activation difficult to diagnosis? It is not single symptom specific…each patient presents with their own constellation of mast cell derived symptoms. There are often coexisting conditions that may mimic mast cell disorders such as IBS, fibromyalgia, eosinophilic esophagitis, headaches, food intolerance, depression.

Here is my Q and A about mast cell activation syndrome with Dr. Matt Hamilton:

Kate: What is mast cell activation syndrome (MCAS) and how does it compare to systemic mastocytosis?

Dr. Hamilton: MCAS is a complex disorder that is poorly understood both in regards to disease mechanisms and clinical manifestations. While the mast cell has been implicated in this disorder that causes many symptoms in multiple organ systems, there may be multiple factors at play. Testing to determine objective evidence of mast cell activation is limited and the mast cells look normal in appearance and number. The syndrome is characterized by what is thought to be abnormal and inappropriate activation of mast cells which produce the characteristic allergy-type symptoms. This syndrome is different from systemic mastocytosis where there is a defined mutation in the mast cell that results in an abnormal number and likely function of mast cells in the various tissues. Patients with mastocytosis may develop organ dysfunction which is not directly observed in patients with MCAS.

Kate: How prevalent is mast cell activation syndrome? Do we know?

Dr. Hamilton: The lack of objective markers to define MCAS and the lack of awareness of this disorder among providers has hampered the ability to accurately assess the prevalence of MCAS in populations. There are about 100,000 people in the United States diagnosed with mastocytosis and specialists who take care of patients with mast cell disorders have said that there may be as many as 10 times the number of mastocytosis patients with MCAS. It is likely that many with MCAS have not sought medical attention or have not been diagnosed with this disorder by their providers.

Kate: What are some symptoms of mast cell activation?

Dr. Hamilton: Mast cells line the surfaces of the GI tract, airway passages and lungs, skin, and other parts of the body that interface with the external environment. Therefore, the predominant symptoms involve these organ systems and include flushing, itching, sweating, and hives in the skin, abdominal pain and cramping, diarrhea, nausea, bloating in the GI tract, and wheezing, shortness of breath, and throat itching in the airway passages. Other common symptoms include palpitations, headache, tingling sensations in the fingers and toes, near fainting, joint pains and bone pains.

Kate: What other disorders do you see in clinical practice that seem to overlap with mast cell activation syndrome?

Dr. Hamilton: There are several medical conditions that are known to overlap with MCAS and these include the connective tissue disorder Ehlers Danlos Syndrome (usually the hypermobility type) and dysautonomia where there are defects in parts of the nervous system that can lead to manifestations such as POTS (lightheadedness and palpitations with standing). There are several other disorders that patients with MCAS may be diagnosed with and these may be truly separate disorders or directly linked to the MCAS. These include chronic fatigue and pain syndromes, anxiety and depression, chemical sensitivities, and chronic lyme disease.

Kate: What testing is requested if MCAS is suspected?

Dr. Hamilton: If one suspects MCAS based on symptom profile, we recommend a serum tryptase, and a 24 hour urine for n-methyl histamine and ll-beta prostaglandin F2 alpha. The first two are available at most labs. In general, the patient should be seen by their PCP about this and then referred to Allergy/Immunology to work up primary allergy sources and consider other diagnoses before labeling as MCAS.

The next Mast Cell Activation Syndrome post (part 2) will include some information from a patient’s perspective along with the potential role of supplements or pharmaceutical treatments. Part 3 will discuss the potential role and application of nutrition and stress management.

Past Posts

20 replies on “Mast Cell Activation Syndrome (Part 1)“

Rachel

Loved this post! It’s so interesting that some of the symptoms of MCAS (abdominal pain, cramping, diarrhea, bloating) look just like IBS symptoms. The immune system is so fascinating – can’t wait to read your next two posts on this topic!

Loretta Bonaccorso

Well, this sure explains a lot ! Is over-reaction to change in temperature included? FE: heat goes on and severe sweating starts immediately; heat goes off and the cold feels like its biting. Thanks for this article, demographism is something I’ve never heard of but have sure experienced it. Can’t wait for the next installment.

Ann Marie Viscuso

Kate, as a former patient I am so glad you are addressing this topic. I struggled for years with the correct diagnosis and then saw Dr Hamilton and Dr Castells at BWH. I finally received the correct diagnosis and have recently found the correct combination of medicines for my body and am almost back to my old self, although I do struggle with eating a balanced diet so look forward to parts 2 and 3 (maybe it’s time to make another appointment).

Mary Ann

Thank you for this. I was diagnosed with Mast Cell Activation Syndrome about one year ago. It took seeing several doctors before being diagnosed. Foods high in histamine especially vinegar and protein that has been allowed to cool (it begins to ferment) are major symptom producers. I look forward to the rest of your series on this!

Teresa

Thanks for the article Kate. If you have MCAS (which I do) or any other GI issue, is it bad for your health to run/exercise if 100% of the time, you feel bloated/GI inflammation afterwards? I am a lifelong runner and marathoner and now I have adverse symptoms after I run. The GI distress goes away within three hours or so but I don’t know if having that obvious inflammation is doing more bad than good. It’s hard to ask conventional doctors who don’t care as much about working out; they simply tell me to stop working out. Any thoughts you have would be appreciated!

Teresa, I typically have my GI and MCAS clients reduce intense exercise initially to calm things down until other symptoms are at stable level -and then try to increase activity slowly to their tolerance. Intense exercise is tough on the gut–as you currently are feeling–and can contribute to intestinal permeability.

Pat S Emmons

Oh my gosh – thanks SO much for doing this series Kate. Although I feel much better going GF and have improved on a low histamine diet (as much as I can manage anyway), I still have many many symptoms of MCAS. I am going to wait to finish this series and go from there. We are so fortunate to have those of you in the medical profession who are studying these little-known/recognized disorders. It has been a 20+ year journey for me. I KNOW it’s not all in my head!!!

Jeanne

Hi Kate, thanks for this article. Do you see MCAS occur with SIBO? I’ve had severe chronic sinus issues, asthma and allergies for years, and was diagnosed with SIBO almost a year ago. When I started on the low FODMAP diet and cut out dairy, alcohol and many processed foods, my sinus issues greatly improved, but I still haven’t been able to successfully get rid of SIBO and the digestive issues long term even after multiple rounds of Xifaxan and herbal treatment. We’ve ruled out a lot of potential root causes for my SIBO, but now I’m starting to wonder about MCAS. I have issues with a lot of the high histamine foods which can be difficult to manage on top of being low FODMAP. Thanks!

Mary

I am fascinated by the current reporting as I had been almost convinced I had mast cell disease years ago; feeling it had been triggered by the cdiff infection. I believe it was before I had started seeing you but one of the doctors I had seen at BIDMC had me do the 24 hour urine test but the results came back that they didn’t feel it was mast cell. Interesting to see so much more information about this though.

Hi Mary,
I think infections including SIBO can provide the ‘perfect storm’ and contribute to onset of mast cell symptoms. It can be a very transient problem for some–and others more chronic….from my experience. Good to hear from you!

Teresa

There is an interesting post by Dr. Tania Dempsey which discusses why there are a great number of false negatives with urine testing. https://www.drtaniadempsey.com/single-post/Ask-The-Expert-Mast-Cell-Activation-Syndrome . Here is an excerpt: many mast cell mediators have very short half-lives and quickly break down when exposed to heat (certainly body heat, and perhaps even room temperature heat). For example, prostaglandin D2 and heparin — both mediators relatively specific to the mast cell — have very short half-lives, on the order of about one minute. Therefore, if the blood or urine specimen in which we intend to measure levels of these mediators is left exposed to heat (even room temperature) for one minute after collection from the patient, one-half of the prostaglandin D2 and heparin in that sample is now gone, leaving one-half of what was originally there. And if the specimen is left unchilled for a second minute, then one-half of the remaining one-half is now gone, leaving only a quarter of what was originally there. You can see how a specimen for prostaglandin D2 or heparin testing doesn’t have to be left unchilled for very long before most of what you’re looking for has disappeared —